title: Peripheral glucagon-like peptide-1 (GLP-1) and satiation.
abstract: Peripheral GLP-1 is produced by post-translational processing of pro-glucagon in enteroendocrine L-cells and is released in response to luminal nutrient (primarily carbohydrate and fat) stimulation. GLP-1 is well known for its potent insulinotropic and gluco-regulatory effects. GLP-1 receptors (GLP-1R) are expressed in the periphery and in several brain areas that are implicated in the control of eating. Both central and peripheral administration of GLP-1 have been shown to reduce food intake. Unresolved, however, is whether these effects reflect functions of endogenous GLP-1. Data collected in our laboratory indicate that in chow-fed rats: 1) Remotely controlled, intra-meal intravenous (IV) or intraperitoneal (IP) GLP-1 infusions selectively reduce meal size; 2) hindbrain GLP-1R activation is involved in the eating-inhibitory effect of IV infused GLP-1, whereas intact abdominal vagal afferents are necessary for the eating-inhibitory effect of IP, but not IV, infused GLP-1; 3) GLP-1 degradation in the liver prevents a systemic increase in endogenous GLP-1 during normal chow meals in rats; and 4) peripheral or hindbrain GLP-1R antagonism by exendin-9 does not affect spontaneous eating. Also, although our data indicate that peripheral GLP-1 can act in two different sites to inhibit eating, they argue against a role of systemic increases in endogenous GLP-1 in satiation in chow-fed rats. Therefore, further studies should examine whether a local paracrine action of GLP-1 in the intestine or and endocrine action in the hepatic-portal area is physiologically relevant for satiation.
authors.affiliation: Physiology and Behaviour Laboratory, Institute of Food, Nutrition and Health, ETH Zurich, 8603 Schwerzenbach, Switzerland.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Punjabi
authors.forename: Myrtha
authors.initials: M
authors.lastname: Arnold
authors.forename: Nori
authors.initials: N
authors.lastname: Geary
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-López
mesh_terms: D000818:Animals; D004435:Eating / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism; D012249:Rhombencephalon / Q000378:metabolism*; D012527:Satiation / Q000502:physiology*
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1